Exposures to humidifier disinfectant and various health conditions in Korean based on personal exposure assessment data of claimants for compensation.

BACKGROUND: Humidifier disinfectants (HDs) were commonly used household chemicals to prevent microbial growth in a humidifier water tank in South Korea. A growing body of evidence has indicated that its airborne exposure can induce severe lung injury. However, there has been low awareness of other health outcomes in HD users. This study aimed to evaluate health conditions appealed by claimants for compensation in relation with an increased exposure to HD. METHODS: From survey data of personal HD exposure assessment of claimants for compensation in Korea, we included a total of 4,179 subjects [cases in each dataset were defined by nine reported health conditions, i.e., pneumonia, asthma, cardiovascular disease, respiratory disease, otorhinolaryngologic disease, brain disease (including cerebrovascular disease), dermatological disease, lung cancer, and all cancers]. HD exposures was considered as the following exposure criteria: exposure duration, exposure proximity, exposure direction, chemical type, cumulative exposure time, indoor air concentration, and cumulative exposure level. Logistic regression models were used to evaluate the associations between HD exposure and health conditions. RESULTS: After adjusting for sociodemographic and health behavioral factors and other chemical exposures (households, environmental, and occupational exposures), an increase in cumulative HD exposure time was significantly associated with risks of all nine diseases (all p-trends < 0.05). An increase in HD exposure duration was associated with asthma, respiratory disease, otorhinolaryngologic disease, dermatological disease, all cancers, and lung cancer (p-trends < 0.05). Indoor HD concentration was associated with only pneumonia (p-trend = 0.015). CONCLUSIONS: Our findings suggest that cumulative exposures to airborne HD might potentially increase the risk of various reported health outcomes.

New-Onset and Exacerbation of Lung Diseases after Short-Term Exposures to Humidifier Disinfectant during Hospitalization.

(1) Background: Humidifier disinfectant (HD) is a biocidal chemical to keep the water tank inside a humidifier clean. Thousands of Koreans have experienced HD-related lung injuries. Of them, 6.9% were exposed to HD in hospitals. (2) Methods: This study investigated changes of diseases in patients (or caregivers) who experienced HD exposures during hospitalization and also investigated characteristics of hospital exposure using data from all HD-related lung injury enrollment in Korea. (3) Results: Of a total of 162 subjects, 139 subjects were hospitalized for non-lung diseases, and 23 people were hospitalized for lung diseases at the time of hospitalization. During hospital exposure, 99 (71.2%) of those hospitalized with non-lung disease experienced a new-onset of lung disease, and 15 (65.2%) of those hospitalized with lung diseases experienced exacerbation of their existing lung diseases. When we compared their exposure characteristics, those exposed in hospitals (vs. non-hospital, mostly home) were exposed for shorter periods, at closer distances, at higher HD indoor concentrations, constantly all day, and directly in the facial direction. (4) Conclusion: In conclusion, HD exposures in hospital with a high intensity even for a short term were associated with new-onset or exacerbation of lung diseases. Our findings suggest that acute exposures to HD can cause lung diseases.

Misclassification and characterization of exposure to humidifier disinfectants using a questionnaire.

BACKGROUND: Lung disease caused by exposure to chemical substances such as polyhexamethylene guanidine (PHMG) used in humidifier disinfectants (HDs) has been identified in Korea. Several researchers reported that exposure classification using a questionnaire might not correlate with the clinical severity classes determined through clinical diagnosis. It was asserted that the lack of correlation was due to misclassification in the exposure assessment due to recall bias. We identified the cause of uncertainty to recognize the limitations of differences between exposure assessment and clinical outcomes assumed to be true value. Therefore, it was intended to check the availability of survey using questionnaires and required to reduce misclassification error/bias in exposure assessment. METHODS: HDs exposure assessment was conducted as a face-to-face interview, using a questionnaire. A total of 5245 applicants participated in the exposure assessment survey. The questionnaire included information on sociodemographic and exposure characteristics such as the period, frequency, and daily usage amount of HDs. Based on clinical diagnosis, a 4 × 4 cross-tabulation of exposure and clinical classification was constructed. When the values of the exposure rating minus the clinical class were ≥ 2 and ≤ - 2, we assigned the cases to the overestimation and underestimation groups, respectively. RESULTS: The sex ratio was similar in the overestimation and underestimation groups. In terms of age, in the overestimation group, 90 subjects (24.7%) were under the age of 10, followed by 52 subjects (14.2%) in their 50s. In the underestimation group, 195 subjects (56.7%) were under the age of 10, followed by 80 subjects (23.3%) in their 30s. The overestimation group may have already recovered and responded excessively due to psychological anxiety or to receive compensation. However, relatively high mortality rates and surrogate responses observed among those under 10 years of age may have resulted in inaccurate exposure in the underestimation group. CONCLUSIONS: HDs exposure assessment using a questionnaire might not correlate with adverse health effects due to recall bias and various other causes such as recovery of injury and psychological anxiety. This study revealed exposure misclassification and characteristics affected by HDs and proposed a questionnaire-based exposure assessment methodology to overcome the limitations of past exposure assessment.

FGF12 (Fibroblast Growth Factor 12) Inhibits Vascular Smooth Muscle Cell Remodeling in Pulmonary Arterial Hypertension.

Loss of BMP (bone morphogenic protein) signaling induces a phenotype switch of pulmonary arterial smooth muscle cells (PASMCs), which is the pathological basis of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Here, we identified FGF12 (fibroblast growth factor 12) as a novel regulator of the BMP-induced phenotype change in PASMCs and elucidated its role in pulmonary vascular remodeling during PAH development. Using murine models of PAH and lung specimens of patients with PAH, we observed that FGF12 expression was significantly reduced in PASMCs. In human PASMCs, FGF12 expression was increased by canonical BMP signaling. FGF12 knockdown blocked the antiproliferative and prodifferentiation effect of BMP on human PASMCs, suggesting that FGF12 is required for the BMP-mediated acquisition of the quiescent and differentiated PASMC phenotype. Mechanistically, FGF12 regulated the BMP-induced phenotype change by inducing MEF2a (myocyte enhancer factor 2a) phosphorylation via p38MAPK signaling, thereby modulating the expression of MEF2a target genes involved in cell proliferation and differentiation. Furthermore, we observed that TG (transgenic) mice with smooth muscle cell-specific FGF12 overexpression were protected from chronic hypoxia-induced PAH development, pulmonary vascular remodeling, and right ventricular hypertrophy. Consistent with the in vitro data using human PASMCs, FGF12 TG mice showed increased MEF2a phosphorylation and a substantial change in MEF2a target gene expression, compared with the WT (wild type) controls. Overall, our findings demonstrate a novel BMP/FGF12/MEF2a pathway regulating the PASMC phenotype switch and suggest FGF12 as a potential target for the development of therapeutics for ameliorating pulmonary vascular remodeling in PAH.

Fibroblast Growth Factor 12 Is a Novel Regulator of Vascular Smooth Muscle Cell Plasticity and Fate.

OBJECTIVE: Vascular smooth muscle cells (VSMCs) modulate their phenotype between synthetic and contractile states in response to environmental changes; this modulation plays a crucial role in the pathogenesis of restenosis and atherosclerosis. Here, we identified fibroblast growth factor 12 (FGF12) as a novel key regulator of the VSMC phenotype switch. APPROACH AND RESULTS: Using murine models and human specimens, we found that FGF12 was highly expressed in contractile VSMCs of normal vessel walls but was downregulated in synthetic VSMCs from injured and atherosclerotic vessels. In human VSMCs, FGF12 expression was inhibited at the transcriptional level by platelet-derived growth factor-BB. Gain- and loss-of-function experiments showed that FGF12 was both necessary and sufficient for inducing and maintaining the quiescent and contractile phenotypes of VSMCs. FGF12 inhibited cell proliferation through the p53 pathway and upregulated the key factors involved in VSMC lineage differentiation, such as myocardin and serum response factor. Such FGF12-induced phenotypic change was mediated by the p38 MAPK (mitogen-activated protein kinase) pathway. Moreover, FGF12 promoted the differentiation of mouse embryonic stem cells and the transdifferentiation of human dermal fibroblasts into SMC-like cells. Furthermore, adenoviral infection of FGF12 substantially decreased neointima hyperplasia in a rat carotid artery injury model. CONCLUSIONS: In general, FGF family members induce a synthetic VSMC phenotype. Interestingly, the present study showed the unanticipated finding that FGF12 belonging to FGF family, strongly induced the quiescent and contractile VSMC phenotypes and directly promoted VSMC lineage differentiation. These novel findings suggested that FGF12 could be a new therapeutic target for treating restenosis and atherosclerosis.

Multiresidue pesticide analysis in Korean ginseng by gas chromatography-triple quadrupole tandem mass spectrometry.

In this study, a new analytical method was developed based on gas chromatography-triple quadrupole tandem mass spectrometry (GC-MS/MS) and used to determine 32 multiclass pesticides in ginseng products. The analytical method was validated, yielding recovery rates in the range of 55.2-108.3%, with precision values expressed as relative standard deviation (RSD) lower or equal to 12% at the spiking levels of 30, 100, and 1000 µg/kg. Correlation coefficients and LOQs (limit of quantification) were in the range 0.9801-0.9989 and 0.15-70 g/kg, respectively. With these validation data and this method, multiresidue pesticides of ginseng samples (fresh ginseng (n=118), red ginseng (n=24), dried ginseng (n=10)) were analysed. Among them, the most frequently detected pesticide was tolclofos-methyl. Tolclofos-methyl was detected in 86.4% of fresh ginseng (18.25-404.5 µg/kg), 91.7% of red ginseng (13.14-119.4 µg/kg), and 87.5% of dried ginseng (23.15-3673 µg/kg).